Twenty-one canine genetic diseases are known to be homologous to human disorders. Therefore, the dog is gaining recognition as a model for studying human genetic diseases, especially those rare recessive disorders with complex inheritance that are difficult to study in human populations. But the dog's unique reproductive characteristics (some of which are similar to the human) make this species difficult to propagate under controlled conditions. Assisted reproductive techniques, including in vitro oocyte maturation (IVM), fertilization (IVF) and embryo transfer could be valuable tools in managing genotypically valuable and rare canids. But little is known about dog oocyte biology, information that is needed to understand regulatory mechanisms that will one day allow successful IVM and IVF at rates comparable to the mouse, rat and the cat. Lack of IVM progress in the dog is related to the uniqueness of its oocyte that is released from the follicle in an immature state and, therefore, matures in the oviduct. The general aim of this proposal is to increase our understanding of the molecular and cellular mechanisms controlling oocyte maturation in the dog. The specific aims include: 1) characterizing intrinsic (oocyte) factors (i.e., transcriptional activity, expression of genes controlling the cell cycle and metabolic activity) regulating maturation; 2) determining the spermatozoon's influence on nuclear maturation; 3) identifying extrinsic (follicular and oviductal) factors affecting meiotic competency; and 4) using this basic knowledge to develop a consistently effective in vitro culture system that results in at least 60% of oocytes achieving metaphase II and 50% fertilizing in culture. These studies of the dog will shed light on new and novel mechanisms that will increase our overall understanding about mammalian oocyte maturation as well as offer insights relevant to the human. For the dog, this scholarly knowledge will be beneficial to advancing in vitro culture and fertilization systems targeting immature oocytes that eventually will be useful in managing and conserving canine genotypes to ensure perpetuation of valuable models long into the future. Finally, this strategy will provide the Candidate multidisciplinary training in the disciplines of molecular and cellular biology, biochemistry and in vitro oocyte culture from a host of world-class scientists that will exponentially increase her expertise and further her career as an independent investigator.